A variety of aromatic- heterocyclic compounds are known to exhibit bronchodilator activity. One of the most widely used compounds for treatment of mammals is theophylline, which has the structure shown below: ##STR1##
Numerous attempts to obtain a safer, more potent bronchodilator have not yet supplanted theophylline.
Pyrimido[5,4-b] oxazines are known compounds which are reported by Sazonov, et al., Khimiya Geterotsiklicheskikh Soedinenii, 1973, 171; ibid., 1972, 1285, and ibid., 1976, 681. These compounds, which have not been described as bronchodilators, have the following structure: ##STR2## wherein R is amino, acetamido, hydrogen or methyl; R' is hydrogen, methyl, hydrazino, piperidino, morpholino, methoxy, methylthio, mercapto, chloro or hydroxy; and R" is hydrogen, methyl, ethyl, propyl, or dimethyl.
Pyrimido[4,5-b][1,4] oxazines are known compounds which are reported by Melik-Ogandzhanyan, et al., Khimiya Geterotsiklicheskikh Soedinenii, 1985, 974. The corresponding 4-chloro, 4-hydroxy, 4-dialkylamino, 4-morpholino and 4-piperidino derivatives are reported. They have the following structure: ##STR3## wherein R is methyl or hydrogen and R' is chloro, hydroxy, N,N-dimethylamino, N,N-diethylamino, morpholino or piperidino. None of the reported compounds were described as bronchodilators.
Some pyrimido[5,4-b][1,4]thiazines are known, reported by E. F. Schroeder and R. M. Dodson, J. Amer. Chem. Soc., 84, 1904-1913 (1962) and by R. N. Henri, R. A. Lazarus and S. J. Benkovic, J. Med. Chem., 26, 559-563 (1983). None of the reported compounds were described as bronchodilators.
U.S. Pat. Nos. 4,477,45? and 4,572,910, respectively, disclose triazolo[4,3-c]pyrimidines and triazolo[1,5-c]pyrimidines which contain a heterocyclic amine moiety such as piperazino, piperidino, morpholino or thiomorpholino on the 5- and/or 7-position of the pyrimidine ring. These compounds are bronchodilators.
Triazolo[1,5-c]pyrimido[4,5-b][1,4]oxazines, triazolo[1,5-c]pyrimido[5,4-b][1,4]oxazines and triazolo[1,5-c]pyrimido[5,4-b][1,4]thiazines have not previously been reported.